PBDE: structure-activity studies for the inhibition of hepatitis C virus NS3 helicase

Kazi Abdus Salam; Atsushi Furuta; Naohiro Noda; Satoshi Tsuneda; Yuji Sekiguchi; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Hidenori Tani; Sona Rani Roy; Junichi Tanaka; Masayoshi Tsubuki; Nobuyoshi Akimitsu

doi:10.3390/molecules19044006

PBDE: structure-activity studies for the inhibition of hepatitis C virus NS3 helicase

Molecules. 2014 Apr 2;19(4):4006-20. doi: 10.3390/molecules19044006.

Authors

Affiliations

¹ Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. salam_bio26@yahoo.com.
² Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. atsushi.5961@ruri.waseda.jp.
³ Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. noda-naohiro@aist.go.jp.
⁴ Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. stsuneda@waseda.jp.
⁵ Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. y.sekiguchi@aist.go.jp.
⁶ Department of Microbiology, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. atsuyay@yamanashi.ac.jp.
⁷ Department of Microbiology, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. kmoriishi@yamanashi.ac.jp.
⁸ Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. nakakoshi@phar.toho-u.ac.jp.
⁹ Research Institute for Environmental Management Technology, National Institute of Advanced Industrial Science and Technology (AIST), 16-1, Onogawa, Tsukuba, Ibaraki 305-8569, Japan. h.tani@aist.go.jp.
¹⁰ Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan. sonarroy@gmail.com.
¹¹ Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan. jtanaka@sci.u-ryukyu.ac.jp.
¹² Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan. tsubuki@hoshi.ac.jp.
¹³ Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. akimitsu@ric.u-tokyo.ac.jp.

Abstract

The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3) is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE) 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1) on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1) against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / antagonists & inhibitors*
Adenosine Triphosphatases / chemistry
Animals
Antiviral Agents / isolation & purification
Antiviral Agents / pharmacology*
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Halogenated Diphenyl Ethers / isolation & purification
Halogenated Diphenyl Ethers / pharmacology*
Hepacivirus / chemistry
Hepacivirus / enzymology
Humans
Porifera / chemistry*
RNA Helicases / antagonists & inhibitors*
RNA Helicases / chemistry
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / chemistry

Substances

Antiviral Agents
Enzyme Inhibitors
Halogenated Diphenyl Ethers
NS3 protein, hepatitis C virus
Viral Nonstructural Proteins
Adenosine Triphosphatases
RNA Helicases